The Importance Of Gene Fusions

Amazing Essays
Deliverables for Specific Aim 2: Any candidate gene identified in AA PCa will be subjected to screening EA PCa cohort. Depending on the nature of the candidate gene we will choose PCR, FISH, IHC and RNA-ISH approach to study the recurrent nature. Our systematic analysis of sequencing data we will address the following questions: Among the many fusion genes in a sample, how many of them are causal aberrations (driver)? How many of them are responsible for tumor growth (passenger)? How do so many abnormal gene fusion products cooperate in a tumor environment? Do they function in a common signaling pathway? The different clinical outcome and available treatment options for each molecular subtype will lead to the development of new diagnostic methods …show more content…
Initially the ETS family gene fusions in prostate cancer was identified by cancer outlier profile analysis (COPA)43 using the gene expression microarray data. Given the unprecedented high prevalence of gene rearrangements and associated gene fusions in prostate cancer, we hypothesized that additional non-ETS gene fusions may occur in the ETS negative prostate cancer. This view is supported by the recent identification of RAF family gene rearrangements44 in a small subset of ETS negative prostate cancer. We have also reported RAF rearrangement in a small subset of gastric cancer (AGTRAP-BRAF) and melanoma (BRAF and RAF1). AKAP9-BRAF in thyroid cancer45 and KIAA1549-BRAF in pilocytic astrocytoma46 have also been reported by others and recently pancreatic acinar cell carcinoma was known to have RAF kinase rearrangements similar to the fusion genes that we identified in prostate cancer but with different tissue specific 5’partner gene27. Similarly “druggable” kinase gene fusion, EML4-ALK47 was identified in 1-5% of non-small cell lung cancer. Based on our experience in using the next generation sequencing technology we believe that transcriptome sequencing is the rational and an unbiased approach for the identification of gene fusions in the ETS negative AA men with prostate cancer44; …show more content…
We found rearrangements only in ERG, ETV1, ETV4 and ETV5 genes with different 5’ partner genes. Many other studies have also reported similar results, suggesting non-ETS gene fusions may occur in ETS negative prostate cancer. Five to ten percent of the cases show overexpression of SPINK1 in ETS negative EA PCa6. To test our hypothesis on the presence of non-ETS gene fusions in PCa we undertook an alternate and unbiased high throughput transcriptome sequencing approach using NGS technology (Illumina ) in a small set of ETS negative samples and identified gene fusions involving BRAF and RAF1 genes in 1-2% of ETS negative prostate cancer44. Although RAF genes are not an outlier gene in PCa, based on our scoring system for nominating driver gene fusions we identified BRAF and RAF1 as the outlier gene fusions in the respective samples (Figure 9). Moreover, in the RAF1 fusion positive samples we identified the balanced reciprocal transcripts (ESRP1-RAF1; RAF1-ESRP1) which is a rare phenomenon not readily detected by conventional approaches. We studied the oncogenic properties of the SLC45A3-BRAF and ESRP1-RAF1 using both in vivo and

Related Documents

  • Decent Essays

    Detailed focus question: What is the process of self-renewal and duplication in breast cancer stem cells through E113, the Wnt-beta catenin signaling pathways and the tumor regulator p53? I. Introduction: To explain the cellular and molecular features of my focus question I will provide background on cancer stem cells, some of the various signaling pathways and breast cancer specifically. A. Cancer Stem Cells (Tumor-initiating cells) 1.…

    • 1133 Words
    • 5 Pages
    Decent Essays
  • Decent Essays

    Importance of studying cancer Cancer is a vastly complex disease exhibiting a plethora of genomic alterations and resulting regulatory failures at the root of its progression. Following the milestone of the Human Genome Project (HGP) era, researchers are now focusing on integrating the rich genome-wide association studies (GWAS), single-nucleotide polymorphism (SNP) data, and identified gene signatures within the in vitro, in vivo and clinical frameworks to further our understanding of the molecular mechanisms of carcinogenesis. More recently, the study of epigenetic changes that occur during carcinogenesis is rapidly deve¬loping into an important research field. For example, epigenetic silencing that occurs through the CpG island methylator…

    • 1631 Words
    • 7 Pages
    Decent Essays
  • Decent Essays

    The Cause Of Cancer

    • 1239 Words
    • 5 Pages

    It is also probable that cancer treatment, or cancer therapeutics, will become predictable with the location, and recognition of tumor biomarkers, allowing for more targeted and effective cancer treatments (Olopade and Pichert, 2001). Further digging into therapeutic and oncogenic effects on repair inhibitors are validated to pinpoint the appropriate targets (Olopade and Pichert, 2001). Cancer genetics in oncology is being greatly improved by the Humane Genome Project. Cancer is caused by the fast progressive accumulation of mutated genes that control cell growth, and this can be seen by genetic testing (Olopade and Pichert, 2001). Although genetic testing is used, it is still not used to it’s full potential in oncology care.…

    • 1239 Words
    • 5 Pages
    Decent Essays
  • Decent Essays

    Heterogeneity Of Cancer

    • 834 Words
    • 4 Pages

    Scientists find out that since pre-invasive cancer cells are highly unstable and potential to spread, those cells should be treated. With a genetically diverse tumor, there is a good chance that a few cells will survive when whole other cells die. With current technology, scientists are able to analyze the individual cancer cells in perspective of evolutionary biology which could help them pinpoint its cancer’s adaption and unlimited growth. When cancer cells reproduce, there is always a risk of error which DNA is mistakenly copied, chromosomes misalign, and break up into wrong cell. The new evolutionary approach, a phylogenetic tree, allows scientists to calculate which genes are more likely to be copied or die and become grow or survive.…

    • 834 Words
    • 4 Pages
    Decent Essays
  • Decent Essays

    To examine whether these candidates are also altered in pancreatic ASC, I will analyze the RNA levels of top targets in pancreatic ASC samples that contain UPF1 mutations. To determine the function of the identified candidates from high-throughput sequencing, I will perform overexpression and knockdown experiments in primary pancreatic cell lines to examine for corresponding gain or loss in proliferation. In addition, I will determine whether overexpression of the candidates transforms primary pancreatic cells. In summary, results from this aim will elucidate the mechanism by which UPF1 mutations promote pancreatic…

    • 1047 Words
    • 4 Pages
    Decent Essays
  • Decent Essays

    These steps include dendritic cells promoting tumor antigens obtained from tumor microenvironments or dead tumor cells, recruitment of activated T-cells to cause responses and circumventing immunosuppression in the tumor microenvironment (Kershaw, Devaud et. 2013). Dendritic cells can present antigens using MHC class I and II molecules by moving to the lymph nodes to expose antigens to T cells upon receiving a stimulus (Vegh , Wang et. 1993). The activated naïve T cells can migrate to region containing antigens and target cancer cells displaying these antigens.…

    • 1172 Words
    • 5 Pages
    Decent Essays
  • Decent Essays

    Provide Statistics. Explain how microarray technology can be used to learn how genetic risks can be identified. ○ What is the purpose of microarray? The microarray technology helps scientists identify the change in cells by comparing gene expression and repression within a normal and cancer cell. ○ Explain the process of microarray In a microarray the mRNA is removed from both the infected and uninfected cell.…

    • 1004 Words
    • 5 Pages
    Decent Essays
  • Decent Essays

    Cancer Stem Cells Essay

    • 756 Words
    • 4 Pages

    Malignant cells with these functional properties have been designated as cancer stem cells (Jordan, et al. 2006). It is possible for cancer stem cells arise from regular stem cells through random mutations. However, studies indicate that cancer stem cells can also arise from mutated progenitor cells that possess replicative ability, but do not have the self-renewal capacity of stem cells (Jordan, et al. 2006).…

    • 756 Words
    • 4 Pages
    Decent Essays
  • Decent Essays

    Furthermore, inferred drug combinations will be analyzed using RNA sequencing of treated tumors for their synergistic action and potential benefits for patients with castration-resistant prostate cancer. Approach…

    • 1661 Words
    • 7 Pages
    Decent Essays
  • Decent Essays

    Gastrointestinal Cancer

    • 1353 Words
    • 6 Pages

    New test such as Colon Cancer Assay, and Oncotype Dx, are being developed to monitor different genes in colon cancer tumors (American Society of Clinical Oncology, 2012). As a result, this can help determine which patients have a higher risk of the cancer spreading (American Society of Clinical Oncology, 2012). Researchers have also created a new test that discovers colon cancer that has spread in nearby lymph nodes (American Society of Clinical Oncology, 2012). This is done by finding a type of RNA found in colon cancer but not in regular lymph node cells (American Society of Clinical Oncology, 2012). In addition, this can help identify which patients might benefit from chemotherapy after surgery (American Society of Clinical Oncology, 2012).…

    • 1353 Words
    • 6 Pages
    Decent Essays

Related Topics